1. Field of the Invention
The present invention relates to alkaloid aminoester derivatives which act as muscarinic receptor antagonists, processes for their preparation, compositions comprising them and therapeutic uses thereof.
2. Discussion of the Background
Quaternary ammonium salts acting as muscarinic (M) receptor antagonist drugs are currently used in therapy to induce bronchodilation for the treatment of respiratory diseases. Examples of well known M receptor antagonists are for instance represented by ipratropium bromide and tiotropium bromide.
Several chemical classes acting as selective M3 receptor antagonist drugs have been developed for the treatment of inflammatory or obstructive airway diseases such as asthma and chronic obstructive pulmonary disease (COPD).
Quinuclidine carbamate derivatives and their use as M3 antagonists are for instance disclosed in WO 02/051841, WO 03/053966 and WO 2008/012290, all of which are incorporated herein by reference in their entireties.
Said M and M3 receptor antagonists are currently administered through inhalation route in order to deliver the drug directly at the site of action, thus limiting the systemic exposure and any undesirable side effect due to systemic absorption. Therefore, it is highly desirable to provide M3 receptor antagonists able to act locally, while having high potency and long duration of action. Said drugs, once adsorbed, are degraded to inactive compounds which are deprived of any systemic side effects typical of muscarinic antagonists.
The co-pending application WO 2010/072338, which is incorporated herein by reference in its entirety, describes azonia-bicyclo[2.2.2]octane compounds acting as muscarinic receptor antagonists, further possessing the above therapeutically desirable characteristics.
However, there remains a need for muscarinic receptor antagonists with even further improved properties.